Evaluation of anticonvulsant activity of QUAN-0806 in various murine experimental seizure models.

摘要

A new quinoline derivative, QUAN-0806 (7-hexyloxy-5-phenyl-1,2,4-triazolo[4,3-alpha]quinoline) was tested for anticonvulsant activity using the maximal electroshock seizure (MES) and the rotarod neurotoxicity (Tox) tests in mice. The MES test showed that QUAN-0806 exhibited higher activity (ED50 = 6.5 mg/kg) and lower toxicity (TD50 = 228.2 mg/kg), resulting in a higher protective index (PI = 35.1) than the reference drugs phenytoin, carbamazepin, phenobarbital, and valproate. In addition, QUAN-0806 was found to exhibit significant oral activity against MES-induced seizures with low oral neurotoxicity in mice. QUAN-0806 was tested in chemically induced models (pentylenetetrazole, PTZ; isoniazid, ISO; 3-mercaptopropionic acid, 3-MPA; and strychnine, STRYC) to further investigate the anticonvulsant activity. QUAN-0806 produced significant antagonistic activity against seizures induced by PTZ, 3-MPA, and ISO, suggesting that QUAN-0806 influences GABAergic neurotransmission by activating glutamate decarboxylase (GAD) or inhibiting (GABA)-a-oxoglutarate aminotransferase (GABA-T) in the brain.